Ammonia → 6-Fluoro-3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 2282541ノート

反応式

HRID 2282541 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:18])=O)=[N:6][CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl.N>C1COCC1.CO.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]3[CH3:18])=[N:9][N:8]=2)[CH:7]=1

参加物

9

反応物 5

HCID 222AmmoniaHCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86687104(S)-2-Methyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

生成物 1

HCID 866871056-Fluoro-3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine収率 89%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of Intermediate 81b (657 mg, 2.60 mmol), Ph3P (1.37 g, 5.21 mmol) and Et3N (1.45 mL, 10.4 mmol) in THF (20 mL) at 0° C. was added hexachloroethane (1.23 g, 5.21 mmol) and the resulting yellow suspension was stirred at RT for 2 h, and at reflux for 19 h. The cooled solution was filtered and concentrated in vacuo. The brown oil was redissolved in MeOH (3 mL) and applied to an SCX-2 cartridge (20 g), washing with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo gave a brown oil. FCC, using 1-5% [2M NH3 in MeOH] in DCM, gave the title compound as a brown oil (542 mg, 89%). LCMS (Method 3): Rt 3.00 min, m/z 235 [MH+].

後処理

  1. temperatureat reflux for 19 h
  2. filtrationThe cooled solution was filtered
  3. concentrationconcentrated in vacuo
  4. dissolutionThe brown oil was redissolved in MeOH (3 mL)
  5. washwashing with MeOH (100 mL)
  6. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  7. concentrationconcentration in vacuo
  8. customgave a brown oil

出典と根拠

ORDレコード
ord-6b8f464355224d129d944b99ec956ddd
出典データセット
uspto-grants-2015_09
特許番号
US09139584B2

反応ノート

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